Multi-pinhole Collimator Research Articles

The clinical utilities of multi-pinhole single photon emission computed tomography.

Single photon emission computed tomography (SPECT) is an important imaging modality for various applications in nuclear medicine. The use of multi-pinhole (MPH) collimators can provide superior resolution-sensitivity trade-off when imaging small field-of-view compared to conventional parallel-hole and fan-beam collimators. Besides the very successful application in small animal imaging, there has been a resurgence of the use of MPH collimators for clinical cardiac and brain studies, as well as other small field-of-view applications. This article reviews the basic principles of MPH collimators and introduces currently available and proposed clinical MPH SPECT systems.

Performance evaluation of a novel multi-pinhole collimator for dopamine transporter SPECT

There is a tradeoff between spatial resolution and count sensitivity in SPECT with conventional collimators. Multi-pinhole (MPH) collimator technology has potential for concurrent improvement of resolution and sensitivity in clinical SPECT of ‘small’ organs. This study evaluated a novel MPH collimator specifically designed for dopamine transporter (DAT) SPECT with a triple-head SPECT camera. Count sensitivity was measured with a 99mTc point source placed on the lattice points of a 1 cm grid covering the whole field-of-view (FOV). Spatial resolution was assessed with a Derenzo type hot rod phantom. An anthropomorphic striatum phantom was scanned with total activity representative of a typical patient scan and different striatum-to-background activity concentration ratios. Recovery of striatum-to-background contrast was assessed by the contrast-recovery-coefficient. Measurements were repeated with double-head SPECT with fan-beam or low-energy-high-resolution-high-sensitivity (LEHRHS) collimators. A patient referred to DAT SPECT because of suspicion of Parkinson’s disease was scanned with both LEHRHS and MPH collimators after a single tracer injection. The axial MPH sensitivity profile was approximately symmetrical around its peak, although it was shifted 7 cm towards the patient to simplify positioning. Peak sensitivity of the triple-head MPH system in the center of the FOV was 620 cps MBq−1 compared to 225 cps MBq−1 for the double-head fan-beam system. Sensitivity of the MPH system decreased towards the edges of the FOV. The full width of the sensitivity profile at 200 cps MBq−1 was 21 cm transaxially and 11 cm axially. In MPH SPECT of the Derenzo phantom all rods with ≥ 5 mm diameter were clearly visible. MPH SPECT improved striatal contrast recovery by ≥ 20% compared to fan-beam SPECT. The patient scan demonstrated good image quality of MPH SPECT with almost PET-like delineation of putamen and caudate nucleus. SPECT with dedicated MPH collimators provides considerable improvement of the resolution-sensitivity tradeoff in DAT SPECT compared to SPECT with fan-beam or LEHRHS collimators.

EXIRAD-3D: Fast automated three-dimensional autoradiography

IntroductionAutoradiography is an established technique for high-resolution imaging of radiolabelled molecules in biological tissue slices. Unfortunately, creating a 3D image from a set of these 2D images is extremely time-consuming and error-prone. MicroSPECT systems provide such 3D images but have a low resolution. Here we present EXIRAD-3D, a fast automated method as an alternative for 3D autoradiography from coupes based on ultra-high resolution microSPECT technology. MethodsEXIRAD-3D uses a very small bore focusing multi-pinhole collimator mounted in a SPECT system with stationary detectors (U-SPECT/CT, MILabs B.V. The Netherlands) using a sample holder with integrated tissue cooling to avoid activity leaking or tissue deformation during the scan. The system performance was experimentally evaluated using various phantoms and tissue samples of animals in vivo injected with technetium-99m and iodine-123. ResultsThe reconstructed spatial resolution obtained with a Derenzo hot rod phantom was 120 μm (or 1.7 nl). The voxel values of a syringe phantom image appear to be uniform and scale linearly with activity. Uptake in tiny details of the mouse knee joint, thyroid, and kidney could be clearly visualized. ConclusionEXIRAD-3D opens up the possibility for fast and quantitative 3D imaging of radiolabelled molecules at a resolution far better than in vivo microSPECT and saves tremendous amounts of work compared to obtaining 3D data from a set of 2D autoradiographs. Advances in knowledge and implications for patient careEXIRAD-3D offers superior image resolution over microSPECT, and it can be a very efficient alternative for autoradiography in pharmaceutical and biological studies.

Joint Optimization of Collimator and Reconstruction Parameters in X-Ray Fluorescence Computed Tomography Using Analytical Point Spread Function and Model Observer.

To jointly optimize collimator design and image reconstruction algorithm in X-ray Fluorescence Computed Tomography (XFCT) for imaging low concentrations of high atomic number (Z) elements in small animal models. Single pinhole (SPH) collimator and three types of multi-pinhole (MPH) collimators were evaluated. MPH collimators with 5, 7, and 9 pinholes using lead, stainless steel and brass were considered. A digital cylindrical phantom (0.5mm3 voxels) of 25mm diameter and 25mm height with a central 5mm diameter and 12.5mm height cylindrical insert containing gold nanoparticles (2:1 insert: background concentration) was modeled. A 125kVp, 2mm Sn filtered x-ray spectrum (0.5 cGy/projection) for gold K-shell XFCT was considered. System matrices were implemented using analytical point spread functions (PSF) for each pinhole collimator. Poisson noise was added to the projection data (16 equiangular views) before image reconstruction using Maximum-Likelihood Expectation-Maximization (ML-EM) algorithm. Signal-present and signal-absent images were generated for the detection task performed by a channelized Hotelling observer (CHO) with 10 Dense Difference-of-Gaussian channels. The area under the curve (AUC) in receiver operating characteristic was used as the image quality metric. A stainless steel focusing type MPH with 7 pinholes and 20 iterations of ML-EM provided the highest AUC. MPH collimators outperformed SPH collimators for XFCT and consistently high AUCs were observed with focusing type MPH designs with 7 pinholes. The combinations of collimator design and image reconstruction parameters that maximized AUC were identified, which could improve the performance of XFCT.

Primary, scatter, and penetration characterizations of parallel-hole and pinhole collimators for I-123 SPECT

Multi-pinhole (MPH) collimators are known to provide better trade-off between sensitivity and resolution for preclinical, as well as for smaller regions in clinical SPECT imaging compared to conventional collimators. In addition to this geometric advantage, MPH plates typically offer better stopping power for penetration than the conventional collimators, which is especially relevant for I-123 imaging. The I-123 emits a series of high-energy (>300 keV, ~2.5% abundance) gamma photons in addition to the primary emission (159 keV, 83% abundance). Despite their low abundance, high-energy photons penetrate through a low-energy parallel-hole (LEHR) collimator much more readily than the 159 keV photons, resulting in large downscatter in the photopeak window. In this work, we investigate the primary, scatter, and penetration characteristics of a single pinhole collimator that is commonly used for I-123 thyroid imaging and our two MPH collimators designed for I-123 DaTscan imaging for Parkinson’s Disease, in comparison to three different parallel-hole collimators through a series of experiments and Monte Carlo simulations. The simulations of a point source and a digital human phantom with DaTscan activity distribution showed that our MPH collimators provide superior count performance in terms of high primary counts, low penetration, and low scatter counts compared to the parallel-hole and single pinhole collimators. For example, total scatter, multiple scatter, and collimator penetration events for the LEHR were 2.5, 7.6 and 14 times more than that of MPH within the 15% photopeak window. The total scatter fraction for LEHR was 56% where the largest contribution came from the high-energy scatter from the back compartments (31%). For the same energy window, the total scatter for MPH was 21% with only 1% scatter from the back compartments. We therefore anticipate that using MPH collimators, higher quality reconstructions can be obtained in a substantially shorter acquisition time for I-123 DaTscan and thyroid imaging.

High resolution and sensitivity gamma camera with active septa. A first Monte Carlo study

Gamma cameras are of great interest due to their high potential in the field of Nuclear Medicine Imaging. They allow for an early diagnosis of reduced size tumors, and also for a wide variety of preclinical studies with the aim of designing more effective treatments against cancer. In this work we propose a significantly improved multi-pinhole collimator gamma camera and perform a first Monte Carlo analysis of its characteristics. Maintaining the configuration of a multi-pinhole collimator with a high degree of overlapping (thus with a high sensitivity), we add a new element, an active septa, that besides acting as a collimator, is able to measure the impact coordinates of the incident photon. This way one is able to unambiguously identify through which pinhole any gamma ray passes before being detected. The result is a high sensitivity and resolution multi-pinhole gamma camera with an arbitrarily large field of view. As a consequence, the final reconstructed image does not suffer from the undesired artifacts or truncation associated to the multiplexing phenomenon. In this study we focus on the development of a system able to visualize in 3D tumors, nodes and metastasis in real time in the operating room with very low dose. We also briefly analyse and propose a novel design for a Single Photon Emission Computed Tomography system.

Validation and Performance Assessment of a Preclinical SiPM-Based SPECT/MRI Insert

A preclinical insert for small animal simultaneous SPECT and MR imaging, in particular for imaging mouse brains, is presented. It consists of ten static magnetic resonance imaging (MRI)-compatible gamma cameras based on tiles of silicon photomultipliers readout by a multichannel ASIC and coupled to 5 cm $\boldsymbol \times $ 5 cm CsI(Tl) scintillators and to an MRI-compatible multipinhole collimator. Calibration and image reconstruction algorithm are illustrated. Mutual compatibility is demonstrated along with imaging performance that is comparable with other non-MR micro-SPECT systems: 0.9 mm tomographic spatial resolution across a transverse field of view of 15.6 mm, 12% energy resolution (at 140 keV), and 1105 cps/MBq sensitivity. Experimental results with phantoms (glass capillaries of 290 $ \mu \text{m}$ diameter and a mini Derenzo) are presented.

Augmenting camera images with gamma detector data

BackgroundSquamous cell carcinoma in the head and neck region is one of the most widespread cancers with high morbidity. Classic treatment comprises the complete removal of the lymphatics together with the cancerous tissue. Recent studies have shown that such interventions are only required in 30% of the patients. Sentinel lymph node biopsy is an alternative method to stage the malignancy in a less invasive manner and to avoid overtreatment. In this paper, we present a novel approach that enables a future augmented reality device which improves the biopsy procedure by visual means.MethodsWe propose a co-calibration scheme for axis-aligned miniature cameras with pinholes of a gamma ray collimating and sensing device and show results gained by experiments, based on a calibration target visible for both modalities.ResultsVisual inspection and quantitative evaluation of the augmentation of optical camera images with gamma information are congruent with known gamma source landmarks.ConclusionsCombining a multi-pinhole collimator with axis-aligned miniature cameras to augment optical images using gamma detector data is promising. As such, our approach might be applicable for breast cancer and melanoma staging as well, which are also based on sentinel lymph node biopsy.

Sentinel lymph node fingerprinting

Background. When locating the sentinel lymph node (SLN), surgeons use state-of-the-art imaging devices, such as a 1D gamma probe or less widely spread a 2D gamma camera. These devices project the 3D subspace onto a 1D respectively 2D space, hence loosing accuracy and the depth of the SLN which is very important, especially in the head and neck area with many critical structures in close vicinity. Recent methods which use a multi-pinhole collimator and a single gamma detector image try to gain a depth estimation of the SLN. The low intensity of the sources together with the computational cost of the optimization process make the reconstruction in real-time, however, very challenging.Results. In this paper, we use an optimal design approach to improve the classical pinhole design, resulting in a non-symmetric distribution of the pinholes of the collimator. This new design shows a great improvement of the accuracy when reconstructing the position and depth of the radioactive tracer. Then, we introduce our Sentinel lymph node fingerprinting (SLNF) algorithm, inspired by MR-fingerprinting, for fast and accurate reconstruction of the tracer distribution in 3D space using a single gamma detector image. As a further advantage, the method requires no pre-processing, i.e. filtering of the detector image. The method is very stable in its performance even for low exposure times. In our ex vivo experiments, we successfully located multiple Technetium 99m (Tc-99m) sources with an exposure time of only one second and still, with a very small L2-error.Conclusion. These promising results under short exposure time are very encouraging for SLN biopsy. Although, this device has not been tested on patients yet, we believe: that this approach will give the surgeon accurate 3D positions of the SLN and hence, can potentially reduce the trauma for the patient.

Evaluation of pinhole collimator materials for micron-resolution ex vivo SPECT

Pinhole collimation is widely recognized for offering superior resolution-sensitivity trade-off in SPECT imaging of small subjects. The newly developed EXIRAD-3D autoradiography technique (MILabs B.V.) based on a highly focusing multi-pinhole collimator achieves micron-resolution SPECT for cryo-cooled tissue samples. For such high resolutions, the choice of pinhole material may have a significant impact on images. Therefore, this paper aims to compare the performance of EXIRAD-3D with lead, tungsten, gold, and depleted uranium pinhole collimators designed such that they achieve equal sensitivities. Performance in terms of resolution is characterized for several radioisotopes, namely 111In (171 keV and 245 keV), 99mTc (140 keV), 201Tl (71 keV), and 125I (27 keV). Using Monte Carlo simulation, point spread functions were generated and their profiles as well as their full-width-at-half-maximum and full-width-at-tenth-maximum were determined and evaluated for different materials and isotopes. Additionally, simulated reconstructions of a Derenzo resolution phantom, validated with experimental data, were judged by assessment of the resolvable rods as well as a contrast-to-noise ratio (CNR) analysis. Our results indicate that using materials with higher photon-stopping power yields images with better CNR for the studied isotopes with improvements ranging from 1.9% to 36.6%. Visual assessment on the reconstructed images suggests that for EXIRAD-3D, the tungsten collimator is generally a good choice for a wide range of SPECT isotopes. For relatively high-energy isotopes such as 111In, using gold inserts can be beneficial.

Tomographic Cherenkov-excited luminescence scanned imaging with multiple pinhole beams recovered via back-projection reconstruction.

Cherenkov-excited luminescence scanned imaging (CELSI) is achieved with a clinical linear accelerator during external beam radiotherapy to map out molecular luminescence intensity or lifetime in tissue. In order to realize a deeper imaging depth with a reasonable spatial resolution in CELSI, we optimized the original scanning procedure to complete this in a way similar to x-ray computed tomography and with image reconstruction from maximum-likelihood expectation maximization and multi-pinhole irradiation for parallelization. Resolution phantom studies showed that a 0.3mm diameter capillary tube containing 0.01nM luminescent nanospheres could be recognized at a depth of 21mm into tissue-like media. Small animal imaging with a 1mm diameter cylindrical target demonstrated that fast 3D data acquisition can be achieved by this multi-pinhole collimator approach to image high-resolution luminescence through a whole animal.

Study of a multi-pinhole collimation system based small-angle neutron scattering instrument at the Compact Pulsed Hadron Source

The neutron flux of the Compact Pulsed Hadron Source (CPHS) is about 2–3 orders of magnitude lower than that of large neutron sources, which means that the beam intensity should be improved to achieve good statistics. Multi-pinhole collimation can be used to obtain a lower Q with an acceptable beam intensity in a very small angle neutron scattering (VSANS) instrument and a higher beam intensity for a larger sample size in a small-angle neutron scattering (SANS) instrument. A new nine-pinhole structure is used in a SANS instrument at CPHS to achieve an acceptable range and resolution of Q and a higher beam intensity compared to single-pinhole collimation. The crosstalk issue associated with multi-pinhole collimation is addressed using an optimized algorithm to achieve a higher safety margin and a larger pinhole size with a higher beam intensity at the sample. Different collimator aperture structures are compared on the basis of their noise production. Experiments are performed to verify the theory of calculating reflection noise from the inner surface of the collimator's aperture and parasitic noise from the beveled collimator structure. From a simulated SANS experiment using cold neutrons in the SANS instrument, it is clarified that multi-pinhole collimators with an opening angle on the downstream side have better performance than those with an opening angle on the upstream side and straight-cut collimators. Compared with a single-pinhole collimation system, a nine-pinhole collimation system increases the intensity at the sample by approximately sevenfold when the sample size is increased by 20-fold for CPHS-SANS, and the signal-to-noise ratio is improved by exploiting a specific collimator aperture structure. Our goal is to install a multi-pinhole collimator based SANS instrument at CPHS in the future, and it is hoped that these results will serve to promote the utilization of multi-pinhole collimation systems at other facilities.

A Geant4-based Monte Carlo study of a benchtop multi-pinhole X-ray fluorescence computed tomography imaging.

BackgroundX-ray fluorescence (XRF) computed tomography (XFCT) has shown promise for molecular imaging of metal nanoparticles such as gold nanoparticles (GNPs) and benchtop XFCT is under active development due to its easy access, low-cost instrumentation and operation.PurposeTo validate the performance of a Geant4-based Monte Carlo (MC) model of a benchtop multi-pinhole XFCT system for quantitative imaging of GNPs.MethodsThe MC mode consisted of a fan-beam x-ray source (125 kVp), which was used to stimulate the emission of XRF from the GNPs, a phantom (3 cm in diameter) which included six or nine inserts (3 mm in diameter), each of which contained the same (1 wt. %) or various (0.08–1 wt. %) concentrations of GNPs, a multi-pinhole collimator which could acquire multiple projections simultaneously and a one-sided or two-sided two-dimensional (2D) detector. Various pinhole diameters (3.7, 2, 1, 0.5 and 0.25 mm) and various particle numbers (20, 40, 80 and 100 billion) were simulated and the results for single pinhole and multi-pinhole (9 pinholes) imaging were compared.ResultsThe image resolution for a 1 mm multi-pinhole was between 0.88 and 1.38 mm. The detection limit for multi-pinhole operation was about 0.09 wt. %, while that for the single pinhole was about 0.13 wt. %. For a fixed number of pinholes, noise increased with decreasing number of photons.ConclusionThe MC mode could acquire 2D slice images of the object without rotation and demonstrated that a multi-pinhole XFCT imaging system could be a potential bioimaging modality for nanomedical applications.

Development of 60 [formula omitted] pitch CdTe double-sided strip detectors for the FOXSI-3 sounding rocket experiment

FOXSI-3 (Focusing Optics X-ray Solar Imager) is an international sounding rocket experiment to observe hard X-rays from the Sun. The previous two flights successfully demonstrated the efficacy of the concept of direct solar imaging in hard X-ray band. For the third launch scheduled in the summer of 2018, we have fabricated a prototype of the CdTe Double-sided Strip Detector.To evaluate the basic performance, laboratory tests were conducted. Energy resolution (FWHM) of 0.8 keV at 13.9 keV and 1.3 keV at 59.5 keV are confirmed. Since the optic angular resolution is finer than the strip pitch of the detector at the focal plane, sub-strip position determination is important to make full use of the high precision of the optic. To test the possibility of sub-strip resolution, we developed a new method of investigating the detector strips with a fine multi-pinhole collimator. The results of the analysis were highly favorable and we confirmed the sub-strip resolution by making sub-strip images of multi-pinholes and flat-irradiation. The spectral uniformity over the detector is also confirmed using the sub-strip image of flat-irradiation.

SPECT/MRI INSERT Compatibility: Assessment, Solutions, and Design Guidelines

In spite of the growing interest in multimodal imaging, and in particular of the consolidation of PET/MRI, the development of simultaneous SPECT/MRI systems is still very limited. SPECT offers potential for multitracer imaging and wider diffusion with respect to PET, but, due to the collimator, poses more stringent challenges on space occupation and MRI compatibility. In this paper, we present a systematic analysis of mutual compatibility between standard 3 T magnetic resonance (MR) scanners and a preclinical SPECT insert composed of a static ring of ten silicon photomultipliers (SiPM)-based gamma cameras. On the MR image quality side, the most critical element is the SPECT tungsten multipinhole collimator, whose distortion of the static field is reduced below 1 ppm thanks to second order shimming. On the SPECT side, MR switching gradients are the most critical source of eddy currents and interferences. Thanks to a board mapping tool, developed for this purpose, the most sensitive tracks and electronic components have been identified and replaced. Shielding, heavy low-pass filtering and star layout of the SiPM high voltage tracks, together with limited use of metallic packages, meshed ground planes, and vias, enabled the preservation of the same energy resolution (14% for 99mTc) during MRI. The design guidelines and the experimental results here reported pave the way to MRI compatibility of the clinical version of this insert.

Comparison of fan beam, slit-slat and multi-pinhole collimators for molecular breast tomosynthesis

Recently, we proposed and optimized dedicated multi-pinhole molecular breast tomosynthesis (MBT) that images a lightly compressed breast. As MBT may also be performed with other types of collimators, the aim of this paper is to optimize MBT with fan beam and slit-slat collimators and to compare its performance to that of multi-pinhole MBT to arrive at a truly optimized design. Using analytical expressions, we first optimized fan beam and slit-slat collimator parameters to reach maximum sensitivity at a series of given system resolutions. Additionally, we performed full system simulations of a breast phantom containing several tumours for the optimized designs. We found that at equal system resolution the maximum achievable sensitivity increases from pinhole to slit-slat to fan beam collimation with fan beam and slit-slat MBT having on average a 48% and 20% higher sensitivity than multi-pinhole MBT. Furthermore, by inspecting simulated images and applying a tumour-to-background contrast-to-noise (TB-CNR) analysis, we found that slit-slat collimators underperform with respect to the other collimator types. The fan beam collimators obtained a similar TB-CNR as the pinhole collimators, but the optimum was reached at different system resolutions. For fan beam collimators, a 6–8 mm system resolution was optimal in terms of TB-CNR, while with pinhole collimation highest TB-CNR was reached in the 7–10 mm range.

Design of multi-pinhole collimator system for SANS based on CPHS neutron source

A new design for Small Angle Neutron Scattering instrument based on utilization of multi-pinhole collimator is presented. The 7-pinhole structure has been proposed for 30 years by Glinka[1]. But due to the crosstalk issue, the SNR is not as high as traditional single pinhole system. Luckily, software nowadays helps us to analyze the system and optimize the parameters of the collimator. With the help of 7-pinhole collimator instead of single-pinhole, we can approach almost one magnitude higher flux than before, which is valuable especially in compact pulsed neutron source, whose flux is a big issue.

Simulations of a Multi-Pinhole SPECT Collimator for Clinical Dopamine Transporter (DAT) Imaging.

SPECT imaging of the dopamine transporter (DAT) is used for diagnosis and monitoring progression of Parkinson's Disease (PD), and differentiation of PD from other neurological disorders. The diagnosis is based on the DAT binding in the caudate and putamen structures in the striatum. We previously proposed a relatively inexpensive method to improve the detection and quantification of these structures for dual-head SPECT by replacing one of the fan-beam collimators with a specially designed multi-pinhole (MPH) collimator. In this work, we developed a realistic model of the proposed MPH system using the GATE simulation package and verified the geometry with an analytic simulator. Point source projections from these simulations closely matched confirming the accuracy of the pinhole geometries. The reconstruction of a hot-rod phantom showed that 4.8 mm resolution is achievable. The reconstructions of the XCAT brain phantom showed clear separation of the putamen and caudate, which is expected to improve the quantification of DAT imaging and PD diagnosis. Using this GATE model, point spread functions modeling physical factors will be generated for use in reconstruction. Also, further improvements in geometry are being investigated to increase the sensitivity of this base system while maintaining a target spatial resolution of 4.5-5 mm.

Preliminary study on X-ray fluorescence computed tomography imaging of gold nanoparticles: Acceleration of data acquisition by multiple pinholes scheme

Gold nanoparticles (GNPs) have recently attracted attention in nanomedicine as novel contrast agents for cancer imaging. A decisive tomographic imaging technique has not yet been established to depict the 3-D distribution of GNPs in an object. An imaging technique known as pinhole-based X-ray fluorescence computed tomography (XFCT) is a promising method that can be used to reconstruct the distribution of GNPs from the X-ray fluorescence emitted by GNPs. We address the acceleration of data acquisition in pinhole-based XFCT for preclinical use using a multiple pinhole scheme. In this scheme, multiple projections are simultaneously acquired through a multi-pinhole collimator with a 2-D detector and full-field volumetric beam to enhance the signal-to-noise ratio of the projections; this enables fast data acquisition. To demonstrate the efficacy of this method, we performed an imaging experiment using a physical phantom with an actual multi-pinhole XFCT system that was constructed using the beamline AR-NE7A at KEK. The preliminary study showed that the multi-pinhole XFCT achieved a data acquisition time of 20 min at a theoretical detection limit of approximately 0.1 Au mg/ml and at a spatial resolution of 0.4 mm.

System geometry optimization for molecular breast tomosynthesis with focusing multi-pinhole collimators

Imaging of 99mTc-labelled tracers is gaining popularity for detecting breast tumours. Recently, we proposed a novel design for molecular breast tomosynthesis (MBT) based on two sliding focusing multi-pinhole collimators that scan a modestly compressed breast. Simulation studies indicate that MBT has the potential to improve the tumour-to-background contrast-to-noise ratio significantly over state-of-the-art planar molecular breast imaging. The aim of the present paper is to optimize the collimator-detector geometry of MBT. Using analytical models, we first optimized sensitivity at different fixed system resolutions (ranging from 5 to 12 mm) by tuning the pinhole diameters and the distance between breast and detector for a whole series of automatically generated multi-pinhole designs. We evaluated both MBT with a conventional continuous crystal detector with 3.2 mm intrinsic resolution and with a pixelated detector with 1.6 mm pixels. Subsequently, full system simulations of a breast phantom containing several lesions were performed for the optimized geometry at each system resolution for both types of detector. From these simulations, we found that tumour-to-background contrast-to-noise ratio was highest for systems in the 7 mm–10 mm system resolution range over which it hardly varied. No significant differences between the two detector types were found.